tbuckley/cabot-search huggingface dataset:
Initial Impact of National CRC Screening on Incidence and Advanced Colorectal Cancer
Authors: Myrtle F. Krul, Marloes A.G. Elferink, Niels F.M. Kok, Evelien Dekker, Iris Lansdorp-Vogelaar, Gerrit A. Meijer, Iris D. Nagtegaal, Emilie C.H. Breekveldt, Theo J.M. Ruers, Monique E. van Leerdam, Koert F.D. Kuhlmann
Journal: Clinical Gastroenterology and Hepatology (2022)
Targeting epigenetic regulators for inflammation: Mechanisms and intervention therapy
Authors: Su Zhang, Yang Meng, Lian Zhou, Lei Qiu, Heping Wang, Dan Su, Bo Zhang, Kui‐Ming Chan, Junhong Han
Journal: MedComm (2022)

Emerging evidence indicates that resolution of inflammation is a critical and dynamic endogenous process for host tissues defending against external invasive pathogens or internal tissue injury. It has long been known that autoimmune diseases and chronic inflammatory disorders are characterized by dysregulated immune responses, leading to excessive and uncontrol tissue inflammation. The dysregulation of epigenetic alterations including DNA methylation, posttranslational modifications to histone proteins, and noncoding RNA expression has been implicated in a host of inflammatory disorders and the immune system. The inflammatory response is considered as a critical trigger of epigenetic alterations that in turn intercede inflammatory actions. Thus, understanding the molecular mechanism that dictates the outcome of targeting epigenetic regulators for inflammatory disease is required for inflammation resolution. In this article, we elucidate the critical role of the nuclear factor-κB signaling pathway, JAK/STAT signaling pathway, and the NLRP3 inflammasome in chronic inflammatory diseases. And we formulate the relationship between inflammation, coronavirus disease 2019, and human cancers. Additionally, we review the mechanism of epigenetic modifications involved in inflammation and innate immune cells. All that matters is that we propose and discuss the rejuvenation potential of interventions that target epigenetic regulators and regulatory mechanisms for chronic inflammation-associated diseases to improve therapeutic outcomes.
Analysis of BRCA2 Copy Number Loss and Genomic Instability in Circulating Tumor Cells from Patients with Metastatic Castration-resistant Prostate Cancer
Authors: Ethan S Barnett, Nikolaus Schultz, Konrad H Stopsack, Ernest T Lam, Andrea Arfe, Jerry Lee, Jimmy L Zhao, Joseph D Schonhoft, Emily A Carbone, Niamh M Keegan, Andreas Wibmer, Yipeng Wang, David B Solit, Wassim Abida, Richard Wenstrup, Howard I Scher
Journal: European Urology (2022)
39P ANV419 is a novel CD122-biased IL-2/anti-IL-2 fusion protein with potent CD8 T cell and NK cell stimulating capacity that shows additive efficacy in combination with checkpoint inhibitors and treatments acting through antibody dependent cellular cytotoxicity
Authors: K. Richter, N. Egli, L. Petersen, P. Murer, A.G. Katopodis, C. Huber
Journal: Annals of Oncology (2022)
Demographic characteristics, factors influencing specialty choice, and intended career goals of graduating medical students pursuing careers in rural dermatology
Authors: Travis S Fulk, Katelyn J Rypka, Laurel L Wessman, Ronda S Farah, Kevin J Gaddis, Robert T Brodell, Cindy Firkins Smith, Matthew D Mansh
Journal: Journal of the American Academy of Dermatology (2022)
Minimising the risk of monkeypox virus transmission during faecal microbiota transplantation: recommendations from a European expert panel
Authors: Gianluca Ianiro, Benjamin H Mullish, Tariq H Iqbal, Elisabeth M Terveer, Simon Mark Dahl Baunwall, Alexander Link, Harry Sokol, Juozas Kupcinskas, Luca Masucci, Maurizio Sanguinetti, Maria J G T Vehreschild, Christian L Hvas, Josbert J Keller, Antonio Gasbarrini, Ed J Kujiper, Giovanni Cammarota
Journal: The Lancet. Gastroenterology & hepatology (2022)
36P Short-term immune check-point inhibitor treatment reduces cardiac pAMPK and IL-10, increases vascular NF-kB expression and serum IL-1, IL-2 and IL-6 levels
Authors: A. Paccone, V. Quagliariello, M. Passariello, S. Buccolo, A. Barbieri, G. Palma, A. Luciano, A. Di Mauro, C. Cipullo, C. De Lorenzo, N. Maurea
Journal: Annals of Oncology (2022)
T cell receptor sequencing reveals reduced clonal breadth of T-cell responses against SARS-CoV-2 after natural infection and vaccination in allogeneic hematopoietic stem cell transplant recipients
Authors: A. Pradier, AC. Mamez, C. Stephan, F. Giannotti, S. Masouridi-Levrat, S. Wang, S. Morin, D. Neofytos, D.L. Vu, A. Melotti, I. Arm, C.S. Eberhardt, J. Tamburini, L. Kaiser, Y. Chalandon, F. Simonetta
Journal: Annals of Oncology (2022)
Models to study basic and applied aspects of lysosomal storage disorders
Authors: Ángel Gaudioso, Teresa P. Silva, María Dolores Ledesma
Journal: Advanced Drug Delivery Reviews (2022)

The lack of available treatments and fatal outcome in most lysosomal storage disorders (LSDs) have spurred research on pathological mechanisms and novel therapies in recent years. In this effort, experimental methodology in cellular and animal models have been developed, with aims to address major challenges in many LSDs such as patient-to-patient variability and brain condition. These techniques and models have advanced knowledge not only of LSDs but also for other lysosomal disorders and have provided fundamental insights into the biological roles of lysosomes. They can also serve to assess the efficacy of classical therapies and modern drug delivery systems. Here, we summarize the techniques and models used in LSD research, which include both established and recently developed in vitro methods, with general utility or specifically addressing lysosomal features. We also review animal models of LSDs together with cutting-edge technology that may reduce the need for animals in the study of these devastating diseases.
Bile Duct Colonization With Enterococcus sp. Associates With Disease Progression in Primary Sclerosing Cholangitis
Authors: Ehud Zigmond, Britta Franziska Zecher, Anna-Lena Bartels, Tomer Ziv-Baran, Thomas Rösch, Guido Schachschal, Ansgar W Lohse, Hanno Ehlken, Christoph Schramm
Journal: Clinical Gastroenterology and Hepatology (2022)
Sequential use of noninvasive ventilation and high flow nasal therapy after early extubation in chest trauma patients recovering from acute hypoxaemic respiratory failure
Authors: G. Accurso, A.N. Cracchiolo, D.M. Palma, G. Misseri, M. Ippolito, V. Alvino, S.M. Raineri, A. Giarratano, A. Cortegiani, C. Gregoretti
Journal: Pulmonology (2022)
Anakinra for refractory pustular psoriasis: A phase II, open-label, dose-escalation trial
Authors: Haley B. Naik, Dominique C. Pichard, Daniella M. Schwartz, Michelle O'Brien, Matthew Masciocchi, Julie Thompson, H. Nida Sen, Seth M. Steinberg, Sandra A. Mitchell, Adriana A. de Jesus, Timothy H. McCalmont, Amit Dey, Rachel K. Rosenstein, Zuoming Deng, Raphaela Goldbach-Mansky, Nehal N. Mehta, Edward W. Cowen
Journal: Journal of the American Academy of Dermatology (2022)
Heart Failure Drug Treatment—Inertia, Titration, and Discontinuation
Authors: Gianluigi Savarese, Takuya Kishi, Orly Vardeny, Samuel Adamsson Eryd, Johan Bodegård, Lars H. Lund, Marcus Thuresson, Biykem Bozkurt
Journal: JACC Heart Failure (2022)

Guidelines recommend early initiation of multiple guideline-directed medical therapies (GDMTs) to reduce mortality/rehospitalization in patients with heart failure and reduced ejection fraction. Understanding GDMT use is critical to improving clinical practice.This study sought to describe GDMT use in Japan, Sweden, and the United States in contemporary real-world settings.EVOLUTION HF (Utilization of Dapagliflozin and Other Guideline Directed Medical Therapies in Heart Failure Patients: A Multinational Observational Study Based on Secondary Data) is an observational cohort study using routine-care databases. Patients initiating any GDMT within 12 months of a hospitalization for heart failure (hHF) discharge were included. Dapagliflozin (the only sodium-glucose cotransporter-2 inhibitor approved at study onset), sacubitril/valsartan, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta-blockers, and mineralocorticoid receptor antagonists (MRAs) were considered separately. Doses and discontinuation were assessed in the 12 months following initiation. Target dose was defined as ≥100% of the guideline-recommended dose.Overall, 266,589 patients were included. Mean times from hHF to GDMT initiation were longer for novel GDMTs (dapagliflozin or sacubitril/valsartan) than for other GDMTs: 39 and 44 vs 12 to 13 days (Japan), 44 and 33 vs 22 to 31 days (Sweden), and 33 and 19 vs 18 to 24 days (United States). Pooled across countries, proportions of patients who discontinued therapy (not including switches from ACE inhibitor or ARB to sacubitril/valsartan) within 12 months were 23.5% (dapagliflozin), 26.4% (sacubitril/valsartan), 38.4% (ACE inhibitors), 33.4% (ARBs), 25.2% (beta-blockers), and 42.2% (MRAs). Corresponding target dose achievements were 75.7%, 28.2%, 20.1%, 6.7%, 7.2%, and 5.1%, respectively.Initiation of novel GDMTs is delayed compared with other GDMTs. Few patients received target doses of GDMTs requiring uptitration. Persistence was higher for dapagliflozin than other GDMTs.
Males induce premature demise of the opposite sex by multifaceted strategies
Authors: Lauren N. Booth, Cheng Shi, Cindy Tantilert, Robin W. Yeo, Jason W. Miklas, Katja Hebestreit, Cecilia N. Hollenhorst, Travis J. Maures, Matthew T. Buckley, Coleen T. Murphy, Anne Brunet
Journal: Nature Aging (2022)

Abstract Interactions between the sexes negatively impact health in many species. In Caenorhabditis , males shorten the lifespan of the opposite sex—hermaphrodites or females. Here we use transcriptomic profiling and targeted screens to systematically uncover conserved genes involved in male-induced demise in C. elegans . Some genes (for example, delm-2 , acbp-3 ), when knocked down, are specifically protective against male-induced demise. Others (for example, sri-40 ), when knocked down, extend lifespan with and without males, suggesting general mechanisms of protection. In contrast, many classical long-lived mutants are impacted more negatively than wild type by the presence of males, highlighting the importance of sexual environment for longevity. Interestingly, genes induced by males are triggered by specific male components (seminal fluid, sperm and pheromone), and manipulating these genes in combination in hermaphrodites induces stronger protection. One of these genes, the conserved ion channel delm-2 , acts in the nervous system and intestine to regulate lipid metabolism. Our analysis reveals striking differences in longevity in single sex versus mixed sex environments and uncovers elaborate strategies elicited by sexual interactions that could extend to other species.
Pet rats as a source of hantavirus in England and Wales, 2013
Authors: L J Jameson, S K Taori, B Atkinson, P Levick, C A Featherstone, G van der Burgt, N McCarthy, J Hart, J C Osborne, A L Walsh, T J Brooks, R Hewson
Journal: Eurosurveillance (2013)

We report the detection of a strain of Seoul hantavirus (SEOV) in pet rats in England and Wales. The discovery followed an investigation of a case of haemorrhagic fever with renal syndrome in Wales. Hantavirus RNA was detected via real-time reverse transcription-polymerase chain reaction (RT-PCR) and classic RT-PCR in pet rats belonging to the patient. Sequencing and phylogenetic analysis confirmed the virus to be a SEOV that is similar, but not identical, to a previously reported United Kingdom strain from wild rats.
Early In Vivo Experience With Tissue-Engineered Trileaflet Heart Valves
Authors: Ralf Sodian, Simon P. Hoerstrup, Jason S. Sperling, Sabine Daebritz, David P. Martin, Adrian M. Moran, Byung S. Kim, Frederick J. Schoen, Joseph P. Vacanti, John E. Mayer
Journal: Circulation (2000)

Background —Tissue engineering is a new approach in which techniques are being developed to transplant autologous cells onto biodegradable scaffolds to ultimately form new functional autologous tissue. Workers at our laboratory have focused on tissue engineering of heart valves. The present study was designed to evaluate the implantation of a whole trileaflet tissue-engineered heart valve in the pulmonary position in a lamb model. Methods and Results —We constructed a biodegradable and biocompatible trileaflet heart valve scaffold that was fabricated from a porous polyhydroxyalkanoate (pore size 180 to 240 μm; Tepha Inc). Vascular cells were harvested from ovine carotid arteries, expanded in vitro, and seeded onto our heart valve scaffold. With the use of cardiopulmonary bypass, the native pulmonary leaflets were resected, and 2-cm segments of pulmonary artery were replaced by autologous cell–seeded heart valve constructs (n=4). One animal received an acellular valved conduit. No animal received any anticoagulation therapy. Animals were killed at 1, 5, 13, and 17 weeks. Explanted valves were examined histologically with scanning electron microscopy, biochemically, and biomechanically. All animals survived the procedure. The valves showed minimal regurgitation, and valve gradients were &lt;20 mm Hg on echocardiography. The maximum gradient was 10 mm Hg with direct pressures. Macroscopically, the tissue-engineered constructs were covered with tissue, and there was no thrombus formation on any of the specimens. Scanning electron microscopy showed smooth flow surfaces during the follow-up period. Histological examination demonstrated laminated fibrous tissue with predominant glycosaminoglycans as extracellular matrix. 4-Hydroxyproline assays demonstrated an increase in collagen content as a percentage of native pulmonary artery (1 week 45.8%, 17 weeks 116%). DNA assays showed a comparable number of cells in all explanted samples. There was no tissue formation in the acellular control. Conclusions —Tissue-engineered heart valve scaffolds fabricated from polyhydroxyalkanoates can be used for implantation in the pulmonary position with an appropriate function for 120 days in lambs.
Prevention of Heart Failure by Antihypertensive Drug Treatment in Older Persons With Isolated Systolic Hypertension
Authors: John B. Kostis
Journal: JAMA (1997)

<h3>Context.</h3> —Heart failure is often preceded by isolated systolic hypertension, but the effectiveness of antihypertensive treatment in preventing heart failure is not known. <h3>Objective.</h3> —To assess the effect of diuretic-based antihypertensive stepped-care treatment on the occurrence of heart failure in older persons with isolated systolic hypertension. <h3>Design.</h3> —Analysis of data from a multicenter, randomized, double-blind, placebo-controlled clinical trial. <h3>Participants.</h3> —A total of 4736 persons aged 60 years and older with systolic blood pressure between 160 and 219 mm Hg and diastolic blood pressure below 90 mm Hg who participated in the Systolic Hypertension in the Elderly Program (SHEP). <h3>Intervention.</h3> —Stepped-care antihypertensive drug therapy, in which the step 1 drug is chlorthalidone (12.5-25 mg) or matching placebo, and the step 2 drug is atenolol (25-50 mg) or matching placebo. <h3>Main Outcome Measures.</h3> —Fatal and nonfatal heart failure. <h3>Results.</h3> —During an average of 4.5 years of follow-up, fatal or nonfatal heart failure occurred in 55 of 2365 patients randomized to active therapy and 105 of the 2371 patients randomized to placebo (relative risk [RR], 0.51; 95% confidence interval [CI], 0.37-0.71;<i>P</i>&lt;.001; number needed to treat to prevent 1 event [NNT], 48). Among patients with a history of or electrocardiographic evidence of prior myocardial infarction (MI), the RR was 0.19 (95% CI, 0.06-0.53;<i>P</i>=.002; NNT, 15). Older patients, men, and those with higher systolic blood pressure or a history of or electrocardiographic evidence of MI at baseline had higher risk of developing heart failure. <h3>Conclusion.</h3> —In older persons with isolated systolic hypertension, stepped-care treatment based on low-dose chlorthalidone exerted a strong protective effect in preventing heart failure. Among patients with prior MI, an 80% risk reduction was observed.
Heparin in the Prevention of Infusion Phlebitis
Authors: Harry W. Daniell
Journal: JAMA (1973)

In a double-blind controlled study of 151 patients admitted to a small coronary care unit, the addition of 1,000 units of beef-lung heparin to each liter of fluid given intravenously was found to reduce the frequency of thrombophlebitis at infusion sites. In 34 patients, 5% dextrose in water containing heparin was infused for a total of 2,243 hours with local inflammation requiring a change in catheter location on three occasions. In 30 patients receiving 5% dextrose in water without heparin, infused for a total of 2,659 hours, 20 changes in catheter location were required. Similar but less striking improvement was associated with heparin administration via catheters receiving 5% dextrose in water plus other medications. Among patients receiving conventional therapeutic doses of heparin by a continuous intravenous drip, infusion phlebitis was rarely present clinically, and polyethylene-catheter viability was greatly prolonged.
Guidelines of the European Respiratory Society and the European Society of Thoracic Surgeons for the management of malignant pleural mesothelioma
Authors: A. Scherpereel, P. Astoul, P. Baas, T. Berghmans, H. Clayson, P. de Vuyst, H. Dienemann, F. Galateau-Salle, C. Hennequin, G. Hillerdal, C. Le Péchoux, L. Mutti, J-C. Pairon, R. Stahel, P. van Houtte, J. van Meerbeeck, D. Waller, W. Weder
Journal: European Respiratory Journal (2009)

Malignant pleural mesothelioma (MPM) is a rare tumour but with increasing incidence and a poor prognosis. In 2008, the European Respiratory Society/European Society of Thoracic Surgeons Task Force brought together experts to propose practical and up-to-dated guidelines on the management of MPM. To obtain an earlier and reliable diagnosis of MPM, the experts recommend performing thoracoscopy, except in cases of pre-operative contraindication or pleural symphysis. The standard staining procedures are insufficient in ∼10% of cases. Therefore, we propose using specific immunohistochemistry markers on pleural biopsies. In the absence of a uniform, robust and validated staging system, we advice use of the most recent TNM based classification, and propose a three step pre-treatment assessment. Patient's performance status and histological subtype are currently the only prognostic factors of clinical importance in the management of MPM. Other potential parameters should be recorded at baseline and reported in clinical trials. MPM exhibits a high resistance to chemotherapy and only a few patients are candidates for radical surgery. New therapies and strategies have been reviewed. Because of limited data on the best combination treatment, we emphasise that patients who are considered candidates for a multimodal approach should be included in a prospective trial at a specialised centre.
HDAC I/IIb selective inhibitor Purinostat Mesylate combined with GLS1 inhibition effectively eliminates CML stem cells
Authors: Qiang Qiu, Linyu yang, Yunyu Feng, Zejiang Zhu, Ning Li, Li Zheng, Yuanyuan Sun, Cong Pan, Huandi Qiu, Xue Cui, Wei He, Fang Wang, Yuyao Yi, Minghai Tang, Zhuang Yang, Yunfan Yang, Zhihui Li, Lijuan Chen, Yiguo Hu
Journal: Bioactive Materials (2022)

Purinostat Mesylate (PM) is a novel highly selective and active HDAC I/IIb inhibitor, and the injectable formulation of PM (PMF) based on the compound prescription containing cyclodextrin completely can overcome PM's poor solubility and improves its stability and pharmacokinetic properties. Here, we showed that PM effectively repressed the survival of Ph+ leukemia cells and CD34+ leukemia cells from CML patients in vitro. In vivo studies demonstrated that PMF significantly prevented BCR-ABL(T315I) induced CML progression by restraining leukemia stem cells (LSCs), which are insensitive to chemotherapy and responsible for CML relapse. Mechanism studies revealed that targeting HDAC I/IIb repressed several important factors for LSCs survival including c-Myc, β-Catenin, E2f, Ezh2, Alox5, and mTOR, as well as interrupted some critical biologic processes. Additionally, PMF increased glutamate metabolism in LSCs by increasing GLS1. The combination of PMF and glutaminase inhibitor BPTES synergistically eradicated LSCs by altering multiple key proteins and signaling pathways which are critical for LSC survival and self-renewal. Overall, our findings represent a new therapeutic strategy for eliminating LSCs by targeting HDAC I/IIb and glutaminolysis, which potentially provides a guidance for PMF clinical trials in the future for TKI resistance CML patients.
Artificial Intelligence in Medicine
Authors: William B. Schwartz, Ramesh S. Patil, Peter Szolovits
Journal: New England Journal of Medicine (1987)

After hearing for several decades that computers will soon be able to assist with difficult diagnoses, the practicing physician may well wonder why the revolution has not occurred. Skepticism at this point is understandable. Few, if any, programs currently have active roles as consultants to physicians. The story behind these unfulfilled expectations is instructive and, we believe, offers hope for the future.Research on computer-aided diagnosis began in the 1960s with high hopes that difficult clinical problems might yield to mathematical formalisms. Most work therefore centered on the application of flow charts, Boolean algebra, pattern matching, and decision analysis to . . .
Long-term outcomes after catheter-based renal artery denervation for resistant hypertension: final follow-up of the randomised SYMPLICITY HTN-3 Trial
Authors: Deepak L Bhatt, Muthiah Vaduganathan, David E Kandzari, Martin B Leon, Krishna Rocha-Singh, Raymond R Townsend, Barry T Katzen, Suzanne Oparil, Sandeep Brar, Vanessa DeBruin, Martin Fahy, George L Bakris, Deepak L Bhatt, George Bakris, Sidney A Cohen, Ralph D'Agostino, Murray Esler, John Flack, David E Kandzari, Barry Katzen, Martin Leon, Laura Mauri, Manuela Negoita, Suzanne Oparil, Krishna Rocha-Singh, Ray Townsend, Ziad Abbud, Tayo Addo, David Anderson, John Angle, Herbert Aronow, Anvar Babaev, Keith Benzuly, Somjot Brar, David Brown, David Calhoun, Paul Casale, Sheldon Chaffer, James Choi, Eugene Chung, Debbie L Cohen, Mark Creager, George Dangas, Harold Dauerman, Shukri David, Mark Davies, Eduardo de Marchena, Ali E Denktas, Chandan Devireddy, William Downey, Mark Dunlap, Daniel Fisher, John Flack, Magdi Ghali, Eric Gnall, Raghava Gollapudi, Mark Goodwin, Nilesh Goswami, Luis Gruberg, Rajiv Gulati, Anuj Gupta, Anjan Gupta, Hitinder Gurm, Jeffrey Hastings, Scott Kinlay, Robert Kipperman, Maurice Buchbinder, Ajay Kirtane, Richard Kovach, David Lee, Samuel Mann, Steven Marso, Fadi Matar, Ernest Mazzaferri, Farrel Mandelsohn, Issam Moussa, Timothy Murphy, Sandeep Nathan, Brian Negus, Sahil Parikh, Manesh Patel, Kirikumar Patel, Basil Paulus, George Petrossian, Alex Powell, Jacek Preibisz, Florian Rader, Otelio Randall, Mahmood Razavi, John Reilly, Jonathan Reiner, Michael Ring, Mark Robbins, Kevin Rogers, Nicolas Ruggiero, Renato Santos, William Little, John Schindler, Thomas Scott, Thomas Shimshak, Mehdi Shishehbor, Mitchel Silver, Jasvindar Singh, Kanwar Singh, David Slovut, Rick G Stoufer, Paul Teirsten, Thomas Todoran, George Vetrovec, Ron Waksman, Yale Wang, Sergio Waxman, Robert Wilkins, Khaled Ziada, Frank Zidar
Journal: The Lancet (2022)